Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
Int J Cancer. 2015 Feb 15;136(4):880-93. doi: 10.1002/ijc.29034. Epub 2014 Jul 1.
ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio=1.84, 95%CI=1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.
ABO 血型血清型 A 已知与胃癌（GC）风险相关，但对于参与 Lewis 抗原形成的 ABO 等位基因和岩藻糖基转移酶（FUT）酶以及基因[以及与幽门螺杆菌（H. pylori）结合和致病性]如何与欧洲人群的 GC 风险相关知之甚少。作者在 EPIC 队列（EPIC-Eurgast 研究）中进行的一项病例对照研究中，对 ABO 和 FUT1-7 基因座的 32 个变异与 GC 风险进行了调查，该研究共包括 365 例病例和 1284 例对照。ABO 中的四个变体（包括 rs505922）和等位基因血型 A（AO+AA，比值比=1.84，95%CI=1.20-2.80）与弥漫型 GC 相关；然而，与其他 ABO 变体的条件模型表明，这些关联主要归因于等位基因血型 A。FUT5 中的一个变体也与弥漫型 GC 相关，FUT2（Se）、FUT3（Le）和 FUT6 中的四个变体（和单倍型）与肠型 GC 相关。此外，ABO 中的一个变体、FUT3 中的两个变体和 FUT6 中的两个变体与对照组的 H. pylori 感染状态相关，其中两个（在 FUT3 和 FUT6 中）与肠型 GC 风险弱相关。没有一个单独的变体超过 Bonferroni 校正的 p 值截止值 0.0016；然而，经过基因基于的置换检验后，两个基因座[FUT3(Le)/FUT5/FUT6 和 FUT2(Se)]分别与弥漫型和肠型 GC 显著相关。因此，建议进行复制和功能研究，以阐明 ABO 和 FUT 等位基因在 H. pylori 感染和亚型特异性胃癌发生中的作用。
